Selective Attenuation by N-0861 ( N 6 -Endonorboran-2-yl-9-Methyladenine) of Cardiac A 1 Adenosine Receptor–Mediated Effects in Humans

Abstract

Background To determine the adenosine receptor subtype selectivity of the novel antagonist N-0861, the A 1 and A 2 receptor–mediated cardiac effects of adenosine were investigated in 13 patients during continuous intravenous infusion and boluses of adenosine before and after intravenous infusion of N-0861. Methods and Results Measurements of the atria-to-His (A-H) interval, chest pain severity, and coronary blood flow velocity were made before and after low-dose (69 μg · kg −1 · min −1 ) intravenous infusion and bolus (2.5 mg) adenosine. Two doses of N-0861 were infused intravenously, and the adenosine protocol was repeated. N-0861 0.25 mg/kg abolished the negative dromotropic effect (A-H interval prolongation) and chest discomfort experienced during infusion of adenosine and attenuated discomfort observed during the boluses of adenosine; however, the increase in coronary blood flow velocity was not significantly affected. Conclusions These actions of N-0861 support the concept that the negative dromotropic effect and anginalike pain caused by adenosine are A 1 adenosine receptor–mediated, whereas the increase in coronary blood flow velocity is due to activation of A 2 adenosine receptors. N-0861 appears to be an effective and selective A 1 adenosine receptor antagonist in humans.